The therapeutic potential of angiotensin-converting enzyme inhibitor enalapril to ameliorate muscle atrophy in a murine model
DOI:
https://doi.org/10.17179/excli2023-6822Keywords:
muscle atrophy, limb immobilization, oxidative stress, enalapril, inflammation, renin-angiotensin systemAbstract
Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P<0.1). Also, inflammatory factors in the enalapril group showed a decrease compared to the atrophy group. The strength of four limbs in the mice of the treatment group (-18.36 ± 1.70 %) was significantly higher than that of the atrophy group (-30.33 ± 3 %) at the end of the atrophy phase and also after 10 days of recovery. The results suggest that the use of enalapril that reduces the activation of angiotensin II-dependent pro-oxidant and pro-inflammatory pathways may improve the functional disorder and muscle necrosis in the murine model of muscle atrophy.
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Copyright (c) 2024 Sima Seifi, Seyedeh Elnaz Nazari, Amir Avan, Nima Khalili-Tanha, Fereshteh Asgharzadeh, Fatemeh Babaei, Ghazaleh Khalili-Tanha, Seyyedeh Zahra Asghari, Mahdieh Darroudi, Gordon A. Ferns, Abdoljalal Marjani, Majid Khazaei
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